U.S. patent number 8,208,137 [Application Number 12/696,853] was granted by the patent office on 2012-06-26 for molecule detection using raman light detection.
This patent grant is currently assigned to Hewlett-Packard Development Company, L.P.. Invention is credited to Alexandre M. Bratkovski, Min Hu, Huei Pei Kuo, Jingjing Li, Zhiyong Li, Fung Suong Ou, Michael Josef Stuke, Michael Renne Ty Tan, Shih-Yuan Wang, Wei Wu.
United States Patent |
8,208,137 |
Hu , et al. |
June 26, 2012 |
**Please see images for:
( Certificate of Correction ) ** |
Molecule detection using Raman light detection
Abstract
An apparatus for detecting at least one molecule using Raman
light detection includes a substrate for supporting a sample
containing the at least one molecule, a laser source for emitting a
laser beam to cause Raman light emission from the at least one
molecule, a modulating element for modulating a spatial
relationship between the laser beam and the substrate at an
identified frequency to cause the Raman light to be emitted from
the at least one molecule at the identified frequency, at least one
detector for detecting the Raman light emitted from the at least
one molecule, and a post-signal processing unit configured to
process the detected Raman light emission at the identified
frequency to detect the at least one molecule.
Inventors: |
Hu; Min (Sunnyvale, CA),
Bratkovski; Alexandre M. (Mountain View, CA), Li;
Jingjing (Palo Alto, CA), Kuo; Huei Pei (Cupertino,
CA), Li; Zhiyong (Redwood City, CA), Ou; Fung Suong
(Palo Alto, CA), Stuke; Michael Josef (Palo Alto, CA),
Tan; Michael Renne Ty (Menlo Park, CA), Wang; Shih-Yuan
(Palo Alto, CA), Wu; Wei (Palo Alto, CA) |
Assignee: |
Hewlett-Packard Development
Company, L.P. (Houston, TX)
|
Family
ID: |
44341398 |
Appl.
No.: |
12/696,853 |
Filed: |
January 29, 2010 |
Prior Publication Data
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|
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Document
Identifier |
Publication Date |
|
US 20110188033 A1 |
Aug 4, 2011 |
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Current U.S.
Class: |
356/301 |
Current CPC
Class: |
G01J
3/44 (20130101) |
Current International
Class: |
G01J
3/44 (20060101) |
Field of
Search: |
;356/301 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Lauchman; Layla
Government Interests
GOVERNMENT LICENSE RIGHTS
The U.S. Government has a paid-up license in this invention and the
right in limited circumstances to require the patent owner to
license others on reasonable terms as provided for by the terms of
(Contract number HR0011-09-3-0002) awarded by the Defense Advanced
Research Projects Agency.
Claims
What is claimed is:
1. A apparatus for detecting at least one molecule using Raman
light detection, said apparatus comprising: a substrate for
supporting a sample containing the at least one molecule; a laser
source for emitting a laser beam to cause Raman light emission from
the at least one molecule; a modulating element for modulating a
spatial relationship between the laser beam and the substrate at an
identified frequency to cause the Raman light to be emitted from
the at least one molecule at the identified frequency; at least one
detector for detecting the Raman light emitted from the at least
one molecule; and a post-signal processing unit configured to
process the detected Raman light emission at the identified
frequency to detect the at least one molecule.
2. The apparatus according to claim 1, wherein the modulating
element is configured to modulate the spatial position of the laser
beam with respect to the substrate at the identified frequency.
3. The apparatus according to claim 2, wherein the laser beam is
configured to be transmitted through an optical waveguide, and
wherein the modulating element comprises a mechanical device
configured to modulate the position of the optical waveguide at the
identified frequency along one or more dimensions.
4. The apparatus according to claim 2, wherein the modulating
element comprises an electro-optic deflector configured to modulate
the spatial position of the laser beam at the identified frequency
along one or more dimensions.
5. The apparatus according to claim 2, wherein the sample comprises
a first molecule at a first location of the substrate and a second
molecule at a second location of the substrate, wherein the
modulating element is configured to modulate the spatial position
of the laser beam between the first location of the substrate and
the second location of the substrate to cause Raman light to be
cyclically emitted from the first molecule and the second molecule
at the identified frequency, and wherein the post-signal processing
unit is configured to process the Raman light emissions at the
identified frequency for each of the first molecule and the second
molecule.
6. The apparatus according to claim 1, wherein the modulating
element is configured to modulate the spatial position of the
substrate with respect to the laser beam along one or more
dimensions.
7. The apparatus according to claim 6, wherein the sample comprises
a first molecule at a first location of the substrate and a second
molecule at a second location of the substrate, wherein the
modulating element is configured to modulate the spatial position
of the substrate to cause the laser beam to cyclically cause Raman
light emission to occur from the first molecule and the second
molecule at the identified frequency, and wherein the post-signal
processing unit is configured to process the Raman light emissions
at the identified frequency for each of the first molecule and the
second molecule.
8. The apparatus according to claim 6, wherein the modulating
element is configured to modulate the spatial position of the
substrate by rotating the substrate at the identified
frequency.
9. The apparatus according to claim 8, wherein the sample comprises
a plurality of molecules positioned in a circular arrangement along
the substrate, wherein the modulating element is configured to
modulate the spatial position of the substrate to cause the laser
beam to cyclically cause Raman light emission to occur from the
plurality of molecules at the identified frequency, and wherein the
post-signal processing unit is configured to process the Raman
light emissions at the identified frequency for the plurality of
molecules.
10. The apparatus according to claim 1, further comprising: an
array of detectors configured to detect Raman light emissions from
a plurality of molecules; and wherein the post-signal processing
unit is configured to process each of the detected Raman light
emissions at the identified frequency.
11. The apparatus according to claim 1, wherein the post-signal
processing unit is further configured to determine a location of
the at least one molecule on the substrate based upon intensities
of the detected Raman light emissions at a plurality of spatial
relationships between the laser beam and the substrate.
12. A method for detecting at least one molecule supported on a
substrate through Raman light detection, said method comprising: is
emitting a laser beam onto the at least one molecule to cause
emission of Raman light from the at least one molecule; modulating
a spatial relationship between the laser beam and the substrate at
an identified frequency to cause the Raman light to be emitted from
the at least one molecule at the identified frequency; detecting
the Raman light emitted from the at least one molecule; and
processing the detected Raman light emission at the identified
frequency to detect the at least one molecule.
13. The method according to claim 12, wherein modulating the
spatial relationship between the laser beam and the substrate
further comprises modulating the spatial position of the laser beam
with respect to the substrate along one or more dimensions.
14. The method according to claim 13, wherein modulating the
spatial position of the laser beam further comprises modulating the
spatial position of the laser beam to cause the laser beam to
modulate between irradiating a first molecule and a second molecule
at the identified frequency, wherein detecting the Raman light
emitted from the at least one molecule further comprises detecting
Raman light emitted from the first molecule and the second
molecule; and wherein processing the detected Raman light emission
further comprises processing the detected Raman light emissions at
the identified frequency for each of the first molecule and the
second molecule.
15. The method according to claim 12, wherein modulating the
spatial relationship between the laser beam and the substrate
further comprises modulating the spatial position of the substrate
with respect to the laser beam along one or more dimensions.
16. The method according to claim 15, wherein modulating the
spatial position of the substrate further comprises modulating the
spatial position of the is substrate to cause the laser beam to
irradiate the first molecule on the second molecule at the
identified frequency, wherein detecting the Raman light emitted
from the at least one molecule further comprises detecting Raman
light cyclically emitted from the first molecule and the second
molecule; and wherein processing the detected Raman light emission
further comprises processing the detected Raman light emissions at
the identified frequency for each of the first molecule and the
second molecule.
17. The method according to claim 15, wherein modulating the
spatial position of the substrate further comprises rotating the
substrate at the identified frequency.
18. The method according to claim 12, further comprising:
determining intensities of the Raman light emissions at a plurality
of respective spatial positions of the laser beam and the
substrate; and determining a location of the least one molecule on
the substrate based upon the determined intensities.
19. A method for detecting a location of at least one molecule with
respect to a substrate through Raman light detection, said method
comprising: emitting a laser beam onto the at least one molecule to
cause emission of Raman light from the at least one molecule;
modulating a spatial relationship between the laser beam and the
substrate to cause a laser spot of the laser beam to modulate with
respect to a position of the at least one molecule; tracking a
position of the laser spot with respect to the substrate during to
the spatial relationship modulation; detecting the Raman light
emitted from the at least one molecule; determining intensities of
the Raman light emitted from the at least one molecule at different
laser spot positions with respect to the substrate; and determining
the location of the at least one molecule based upon the determined
intensities and the laser spot positions.
20. The method according to claim 19, wherein determining the
location of the at least one molecule further comprises determining
the location of the at least one molecule to correspond to the
laser spot position having the substantially highest Raman light
intensity.
Description
BACKGROUND
Raman spectroscopy has been utilized for a number of years to
identify single molecules from various types of samples. Raman
spectroscopy, more particularly, has been utilized to identify the
vibrational modes of molecules to distinguish between different
molecular species. The probability, however, of a Raman interaction
occurring between an excitatory beam of light and an individual
molecule in a sample is very low, for instance, 10.sup.3.degree.
cm.sup.2 for CN. As such, the use of Raman spectroscopy to identify
individual molecules has been relatively limited.
One approach to enhancing the Raman spectroscopy effect is to place
the molecules near roughened silver surfaces. The surface enhanced
Raman spectroscopy (SERS) effect is related to the phenomenon of
plasmon resonance, in which metal nanoparticles exhibit an
increased optical resonance in response to incident electromagnetic
radiation, due to the collective coupling of conduction electrons
in the metal. Attempts at implementing SERS have included coating
metal nanoparticles or fabricating rough metal films on the surface
of the substrate and then applying a sample to the metal-coated
surface.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments are illustrated by way of example and not limited in
the following figure(s), in which like numerals indicate like
elements, in which:
FIG. 1 a simplified schematic diagram of an apparatus for detecting
at least one molecule in a sample using Raman light detection,
according to an embodiment of the invention;
FIGS. 2A and 2B, respectively, illustrate simplified and enlarged
schematic diagrams of the sample depicted in FIG. 1, according to
embodiments of the invention;
FIG. 3 illustrates a simplified schematic diagram of an array of
molecules disposed around a circular substrate, according to an
embodiment of the invention;
FIGS. 4A and 4B, respectively, illustrate simplified and enlarged
diagrams of the detector(s) depicted in FIG. 1 formed of an array
of detectors, according to embodiments of the invention;
FIG. 5 illustrates a simplified schematic diagram depicting a
relationship between Raman light intensity and position along a
substrate, according to an embodiment of the invention;
FIG. 6 shows a flow diagram of a method for detecting at least one
molecule supported on a substrate using Raman light detection,
according to an embodiment of the invention
FIG. 7 shows a flow diagram of a method for detecting a location of
at least one molecule with respect to a substrate through Raman
light detection, according to an embodiment of the invention;
and
FIG. 8 shows a schematic representation of a computing device
configured in accordance with embodiments of the present
invention.
DETAILED DESCRIPTION
For simplicity and illustrative purposes, the principles of the
embodiments are described by referring mainly to examples thereof.
In the following description, numerous specific details are set
forth in order to provide a thorough understanding of the
embodiments. It will be apparent however, to one of ordinary skill
in the art, that the embodiments may be practiced without
limitation to these specific details. In other instances, well
known methods and structures are not described in detail so as not
to unnecessarily obscure the description of the embodiments.
Disclosed herein is an apparatus for detecting at least one
molecule in a sample with a relatively high level of precision
through improved processing of Raman light emissions from the at
least one molecule. The accuracy of the molecule detection is
relatively high because the apparatus disclosed herein
significantly increases the signal-to-noise ratio in the processing
of the Raman light emissions. As discussed in greater detail herein
below, a spatial relationship between a laser beam that causes the
molecule to emit Raman light and a substrate on which the molecule
is supported is modulated at an identified frequency. In addition,
a post-signal processing unit is configured to process the detected
Raman light emitted from the molecule at the identified frequency.
In one regard, the post-signal processing unit or a computing
device is configured to lock into the identified frequency and to
filter out signals in other frequencies when processing the
detected Raman light, which results in the increased
signal-to-noise ratio.
According to an embodiment, the apparatus disclosed herein is
implemented to modulate a spatial relationship between the laser
beam and the substrate to cause the laser beam to illuminate
multiple molecules during a single modulation cycle. The apparatus
is also configured to concurrently detect and process the Raman
light emitted by the multiple molecules.
According to another embodiment, the apparatus disclosed herein is
implemented to determine the locations of one or more molecules
with respect to a substrate. In this embodiment, the apparatus is
configured to detect the intensity levels of the Raman light
emitted by the one or more molecules as the spatial relationship
between the laser beam and the substrate is modulated. In addition,
the intensity levels may be evaluated to determine which location
along one or more dimensions of the substrate resulted in the
substantially highest intensity level and that location may be
determined as the location of the molecule.
With reference first to FIG. 1, there is shown a simplified
schematic diagram of an apparatus 100 for detecting at least one
molecule in a sample using Raman light detection, according to an
embodiment. It should be understood that the apparatus 100 depicted
in FIG. 1 may include additional components and that some of the
components described herein may be removed and/or modified without
departing from a scope of the apparatus 100. It should also be
understood that the components depicted in FIG. 1 are not drawn to
scale and thus, the components may have different relative sizes
with respect to each other than as shown therein.
As shown, the apparatus 100 includes a laser source 102 configured
to continuously emit a laser beam 104, which may have, for
instance, a wavelength of around 400-600 nm. The laser beam 104 is
transmitted through a waveguide 106, such as an optical fiber,
prior to irradiating a sample 112 of one or more molecules 114
contained on a substrate 110. Although not explicitly shown, the
laser beam 104 may traverse an optical path containing one or more
optical devices configured to manipulate, for instance, the
direction, intensity, etc., of the laser beam 104.
As further shown in FIG. 1, the laser beam 104 is configured to
illuminate a molecule 114 and cause a Raman effect on the molecule
114 and thereby cause Raman light to be emitted or scattered from
the molecule 114. The Raman light emitted 116 from the molecule 114
is collected by one or more optical elements 118. The optical
elements 118 may include, for instance, a condenser lens system, a
spectrometer, a filter, etc. For instance, the emitted Raman light
116 is focused by the condenser lens system and undergoes
wavelength dispersion in the spectrometer prior to reaching one or
more optical detectors 120 to, for instance, convert the emitted
Raman light 116 to a monochromated light. The optical detector(s)
120 receives the emitted Raman light 116 and converts it to an
electrical output signal 122, which is transmitted to a post-signal
processing unit 124. Although not shown, the electrical output
signal 122 may be amplified prior to or during transmission to the
post-signal processing unit 124.
The components of the apparatus 100 may be arranged in any suitable
manner. For instance, the optical elements 118 and the detector(s)
120 may be arranged on the same side of the molecule 114 as the as
laser beam 104. In another example, the substrate 110 may comprise
a transparent substrate, such as glass, and the optical elements
118 and the detector(s) 120 may be arranged to capture Raman light
116 that is emitted through the substrate 110.
Also depicted in FIG. 1 is a modulating element 130 for modulating
a spatial relationship between the laser beam 104 and the substrate
110. The modulating element 130 may be configured to modulate the
spatial relationship between the laser beam 104 and the substrate
110 at an identified frequency to cause the Raman light 116 to be
emitted from the molecule 114 at the identified frequency. In one
example, the amplitude of the modulation is selected to enable the
laser beam 104 to intermittently irradiate the molecule 114 during
a modulation cycle. Thus, in an example in which the laser beam 104
has a diameter of 1.lamda., the amplitude of the modulation is set
to be at least 1.lamda..
As discussed in greater detail herein below, the modulating element
130 is configured to modulate either or both the spatial position
of the laser beam 104 and the substrate 110 to effectuate the
spatial relationship modulation between the laser beam 104 and the
substrate 110. In any regard, the post-signal processing unit 124
is configured to process the detected Raman light emission 116 at
the identified frequency to, for instance, determine the species of
the molecule 114.
In one regard, the post-signal processing unit 124 is configured to
implement a lock-in detection technique on the detected Raman light
emission 116 at the identified frequency. As such, for instance,
the post-signal processing unit 124 includes a lock-in amplifier, a
boxcar amplifier, or the like, which serves to detect and amplify
only the signal component of the electrical output signal 122 from
the detector(s) 120 that has the same frequency as that of the
identified frequency at which the modulating element 130 modulates
the either or both of the laser beam 104 and the substrate 110.
Because the post-signal processing unit 124 detects and amplifies
only the signal component of the electrical output signal 122 that
has the same frequency as that of the identified frequency of a
reference signal 132 received from the modulating element 130, the
input signal component having a frequency different from that of
the reference signal 132 is not sampled. Further, by selecting
appropriately the locked-in phase, the post-signal processing unit
124 may sample the signal component ascribable to a particular
molecule 114.
With reference now to FIG. 2A, there is shown a simplified and
enlarged schematic diagram 200 of the sample 112 depicted in FIG.
1, according to an embodiment. The diagram 200 generally depicts a
manner in which the spatial relationship between the laser beam 104
and the substrate 110 is modulated. As shown therein, the spatial
relationship between the laser beam 104 and the substrate 110 is
configured to modulate between a first position "A" and a second
position "B". More particularly, the first position "A" results in
a laser beam A 202 irradiating a first laser spot A 210 and the
second position "B" results in the laser beam B 204 irradiating a
second laser spot B 212. In the example depicted in FIG. 2A, the
first position A on the sample 112 contains a molecule 214, but the
second position B does not contain a molecule of interest. Thus,
for instance, another molecule of the sample 112 or the substrate
110 other than a molecule of interest may be contained at the
second position B.
When the laser spot A 210 irradiates the first position A, the
molecule 214 emits a first Raman light A 220 that is processed as
discussed above with respect to FIG. 1. Likewise, when the laser
spot B 212 irradiates the second position B, a Raman light B 222 is
emitted from a substance that is not a molecule of interest. The
emitted Raman light B 222 is also processed as discussed above. In
this embodiment, the Raman light B 222 emitted from a location that
does not contain a molecule of interest is processed to determine a
background noise level of the sample 112 or the substrate 110. In
addition, the post-signal processing unit 124 or other processing
device, such as a computer device, may utilize the determined
background noise level in improving the signal-to-noise ratio of
the signal received from the Raman light emitted 220 from the
molecule 214.
According to another embodiment, the apparatus 100 is implemented
to concurrently detect multiple molecules as the spatial
relationship between the laser beam 104 and the substrate 110 is
modulated. In this embodiment, and with particular reference to the
diagram 250 in FIG. 2B, a molecule 216 of interest is located at
the second location B. In addition, the molecule 216 emits a Raman
light B 222 when the laser spot 212 is in the second location B.
Moreover, the post-signal processing unit 124 or other processing
device, such as a computer device, may parallel process the Raman
light emissions 220 and 222 received from the molecules 214 and
216, for instance, to detect the molecular species of both of the
molecules 214 and 216.
In the embodiments depicted in FIGS. 2A and 2B, although the laser
spots 210 and 212 have been discussed as moving along a single
dimension, it should be understood that the spatial relationship of
the laser beam 104 and the substrate 110 may instead be modulated
along multiple dimensions. For instance, the spatial relationship
may be modulated in both the x and y directions to enable the laser
beam 104 to illuminate more than two molecules 114 during a single
modulation cycle.
By way of particular example, and with reference to FIG. 3, there
is shown a simplified schematic diagram 300 of an array of
molecules 302 disposed around a circular substrate 310. As shown
therein, at a first time, the laser beam 104 forms a laser spot 108
on one of the molecules 304 causing a Raman light 116 to be emitted
therefrom. At a second time, either or both of the substrate 310
and the laser beam 104 is modulated (as indicated by the arrow 312)
to cause the laser spot 108 to irradiate another molecule 304 of
the array 302 or a location that does not contain a molecule of
interest. At the second time, another Raman light 116 is emitted
from the another molecule 304 or another substance. This process
may be continuously repeated as the relative spatial position of
the laser beam 104 with respect to the substrate 310 is
continuously modulated.
The relative spatial position of the laser beam 104 with respect to
the substrate 310 in FIG. 3 is modulated at an identified
frequency. In addition, the post-signal processing unit 124 (FIG.
1) is configured to process the detected Raman light emissions 116
from the molecules 304 and in certain embodiments, the detected
Raman light emissions 116 from other substances, as discussed
above. As such, the post-signal processing unit 124 may be
configured to continuously and concurrently process multiple
molecules.
With reference back to FIG. 1, the modulating element 130 is
depicted as having multiple alternatives for modulating the spatial
relationship between the laser beam 104 and the substrate 110 at an
identified frequency (as noted by the dashed and full arrows
between the waveguide 106 and the optical elements 118). In a first
alternative 140, the modulating element 130 comprises an
electro-optic deflector configured to modulate the spatial position
of the laser beam 104 at the identified frequency along one or more
dimensions to thereby modulate the position of the laser spot 108
with respect to the substrate 110. In a second alternative 142, the
modulating element 130 is configured to modulate the spatial
position of the optical waveguide 106 to thereby modulate the
position of the laser spot 108. In a third alternative 144, the
modulating element 130 is configured to modulate the spatial
position of the substrate 110 with respect to the laser beam 104 to
thereby modulate the spatial position of the laser spot 104 with
respect to the substrate 110.
In the second and third alternatives 142 and 144, the modulating
element 130 may comprise any suitable mechanical device configured
to modulate either or both of the optical waveguide 106 and the
substrate 110. Examples of suitable mechanical devices include MEMS
devices, piezoelectric devices, a voice coil, etc.
According to another embodiment, the one or more detectors 120
comprise at least one wide area detector configured to detect the
laser spots 108 at multiple displacements. In addition or
alternatively, and with particular reference to FIG. 4A, there is
shown a simplified and enlarged diagram 400 of the detector(s) 120
formed of an array of detectors 402, according to an embodiment.
The array of detectors 402 may be formed of a plurality of
detectors, in which each of the detectors is configured to detect
light received from a different location with respect to the
substrate 110. Also shown therein is a diffraction grating 404
which splits and diffracts the Raman light emissions 410 into
several beams that travel into different directions and onto the
deflectors of the detector array 402. Moreover, the detectors in
the detector array 402 are configured to send electrical output
signals 406 to the post-signal processing unit 124 as discussed
above with respect to the detector(s) 120 in FIG. 1.
Turning now to FIG. 4B, there is shown a simplified and enlarged
diagram 450 of the detector(s) 120 formed of an array of detectors
402, according to another embodiment. As shown therein, instead of
being diffracted by a single diffraction grating 404 as in the
diagram 400, in the diagram 450, the Raman light emissions 410 are
diffracted by multiple diffraction gratings 452-456 prior to
reaching the detector array 402. The multiple diffraction gratings
452-456 generally operate to increase the spacing between the Raman
light emissions 410 to thus enable relatively larger detectors in
the detector array 402 to be implemented in detecting the Raman
light emissions 410 from multiple locations on the substrate 110.
The detectors in the detector array 402 are also depicted as being
configured to send electrical output signals 406 to the post-signal
processing unit 124 as discussed above with respect to the
detector(s) 120 in FIG. 1.
According to another embodiment, the post-signal processing unit
124 or other computing device is configured to determine a location
of at least one molecule 114 based upon intensities of the detected
Raman light emissions 116 detected at different spatial
relationships between the laser beam 104 and the substrate 110.
More particularly, for instance, and with reference to FIG. 5, the
intensities of the Raman light emissions 116 may be tracked with
respect to various positions of the substrate 110. As shown in FIG.
5, the location of the molecule 114 is depicted as being determined
along an X-axis (x-position), but it should be understood that
similar techniques may be implemented to determine the location of
the molecule 114 along a Y-axis (y-position) to thereby determine a
two-dimensional location of the molecule 114.
As shown in the diagram 500 of FIG. 5, the intensity of the Raman
light emission varies depending upon which location of the
substrate 110 is irradiated by a laser spot 108. Thus, by tracking
the intensities of the Raman light emissions 116 with respect to
the substrate 110, a Gaussian profile 510 may be developed and a
location on the Gaussian profile 510 where the intensity level
peaks 520 may be determined. This location of the intensity level
peak 520 may be translated into a particular location in either one
or two dimensions with respect to the substrate 110. In one regard,
the identified locations of one or more molecules 114 may be
employed to more accurately position the laser beam 104 onto the
one or more molecules 114 during a determination operation of the
one or more molecules 114.
Turning now to FIG. 6, there is shown a flow diagram of a method
600 for detecting at least one molecule 114 supported on a
substrate 110 using Raman light detection, according to an
embodiment. It should be understood that the method 600 depicted in
FIG. 6 may include additional steps and that some of the steps
described herein may be removed and/or modified without departing
from a scope of the method 600.
At step 602, a laser beam 104 is emitted onto at least one molecule
114 supported on a substrate 110.
At step 604, a spatial relationship between the laser beam 104 and
the substrate 110 is spatially modulated at an identified frequency
to cause the Raman light to be emitted 116 from the at least one
molecule at the identified frequency. As discussed above, the
spatial relationship may be modulated by modulating the laser beam
104 and/or the substrate 110 through use of any of a number of
different types of modulating elements 130. As also discussed
above, the spatial modulation may cause the laser beam 104 to
irradiate one or more molecules during the modulation.
At step 606, the Raman light emitted 116 from the at least one
molecule 114 is detected through operation of, for instance, the
optical element(s) 118 and the detector(s) 120. As discussed above,
the detector(s) 120 may comprise an array of detectors 402
configured to detect Raman light emitted 116 from molecules 114
located in multiple locations on the substrate 110.
At step 608, the detected Raman light emission(s) 116 are processed
at the identified frequency to detect the molecule(s) 114. More
particularly, for instance, a lock-in detection technique may be
implemented on the detected Raman light emission(s) 116 at the
identified frequency to thus enable the post-signal processing unit
124 to sample only the signal component ascribable to the
molecule(s) 114.
With reference now to FIG. 7, there is shown a flow diagram of a
method 700 for detecting a location of at least one molecule 114
with respect to a substrate 110 through Raman light detection,
according to an embodiment. It should be understood that the method
700 depicted in FIG. 7 may include additional steps and that some
of the steps described herein may be removed and/or modified
without departing from a scope of the method 700.
At step 702, a laser beam 104 is emitted onto at least one molecule
114 supported on a substrate 110.
At step 704, a spatial relationship between the laser beam 104 and
the substrate 110 is modulated to cause a laser spot 108 of the
laser beam 104 to modulate with respect to a position of the at
least one molecule. The spatial relationship may be modulated by
the modulating element 130 as discussed above.
At step 706, a position of the laser spot 108 with respect to the
substrate 110 is tracked during the spatial relationship
modulation. The position of the laser spot 108 with respect to the
substrate 110 may be tracked through use of any suitable tracking
implementation. For example, in instances where the position of the
laser beam 104 is modulated, the settings of one or more optical
devices that affect the location of the laser spot 108 may be
tracked. As another example, in instances where the position of the
substrate 110 is modulated, an encoder may be used to track to the
position of the substrate 110.
At step 708, the Raman light emitted 116 from the at least one
molecule 114 is detected through operation of, for instance, the
optical element(s) 118 and the detector(s) 120. As discussed above,
the detector(s) 120 may comprise an array of detectors 402
configured to detect Raman light emitted 116 from molecules 114
located in multiple locations on the substrate 110.
At step 710, the intensities of the Raman light 116 emitted at the
different laser spot 108 positions with respect to the substrate
110 are determined, for instance, by the post-signal processing
unit 114 or another computing device.
At step 712, the location(s) of the at molecule(s) are determined
based upon the determined intensities and the laser spot 108
positions. More particularly, for instance, a Gaussian profile 510
(FIG. 5) correlating the intensities of the emitted Raman light 116
with respect to different locations on the substrate 110 may be
generated. In addition, a peak intensity location 520 along the
Gaussian profile 510 may be identified and the position on the
substrate 110 corresponding to the peak intensity location 520 may
be determined as the location of the molecule(s) 114.
The methods 600 and 700 employed to detect at least one molecule
114 and to detect a location of at least one molecule 114 with
respect to a substrate 110 may be implemented by a computing
device, which may be a desktop computer, laptop, server, etc.
Turning now to FIG. 8, there is shown a schematic representation of
a computing device 800 configured in accordance with embodiments of
the present invention. The device 800 includes one or more
processors 802, such as a central processing unit; one or more
display devices 804, such as a monitor; a laser source interface
806; a modulating element interface 808; a post-signal processing
unit interface 810; one or more network interfaces 812, such as a
Local Area Network LAN, a wireless 802.11x LAN, a 3G mobile WAN or
a WiMax WAN; and one or more computer-readable mediums 814. Each of
these components is operatively coupled to one or more buses 816.
For example, the bus 816 may be an EISA, a PCI, a USB, a FireWire,
a NuBus, or a PDS.
The computer readable medium 814 may be any suitable medium that
participates in providing instructions to the processor 802 for
execution. For example, the computer readable medium 810 can be
non-volatile media, such as an optical or a magnetic disk; volatile
media, such as memory; and transmission media, such as coaxial
cables, copper wire, and fiber optics. Transmission media can also
take the form of acoustic, light, or radio frequency waves.
The computer-readable medium 810 may also store an operating system
818, such as Mac OS, MS Windows, Unix, or Linux; network
applications 820; and a molecule detection application 822. The
operating system 818 may be multi-user, multiprocessing,
multitasking, multithreading, real-time and the like. The operating
system 818 may also perform basic tasks such as recognizing input
from input devices, such as a keyboard or a keypad; sending output
to the display 804, the laser source 102, the modulating element
130, and the post-signal processing unit 124; keeping track of
files and directories on medium 814; controlling peripheral
devices, such as disk drives, printers, image capture device; and
managing traffic on the one or more buses 816. The network
applications 820 include various components for establishing and
maintaining network connections, such as software for implementing
communication protocols including TCP/IP, HTTP, Ethernet, USB, and
FireWire.
The molecule detection application 822 provides various software
components for detecting molecules 114 and locations of molecules
114, as described above. In certain embodiments, some or all of the
processes performed by the molecule detection application 822 may
be integrated into the operating system 818. In certain
embodiments, the processes can be at least partially implemented in
digital electronic circuitry, or in computer hardware, firmware,
software, or in any combination thereof.
What has been described and illustrated herein is an embodiment
along with some of its variations. The terms, descriptions and
figures used herein are set forth by way of illustration only and
are not meant as limitations. Those skilled in the art will
recognize that many variations are possible within the spirit and
scope of the subject matter, which is intended to be defined by the
following claims--and their equivalents--in which all terms are
meant in their broadest reasonable sense unless otherwise
indicated.
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